Exp Mol Med.  2006 Dec;38(6):625-633.

p53 overexpression represses androgen-mediated induction of NKX3.1 in a prostate cancer cell line

• Jiang A
• Yu C
• Zhang P
• Chen W
• Liu W
• Hu X
• Zhang J

Abstract

Prostate cancer is a disease involving complicated multiple-gene alterations. Both NKX3.1 and p53 are related to prostate cancer and play crucial roles in prostate cancer progression. However, little is known about the relationships and interactions between p53 and NKX3.1 in prostate cancer. We found that NKX3.1 expression is down-regulated by over-expression of wild type (wt) p53 in prostate cancer LNCaP cells. NKX3.1 is down-regulated at both the mRNA and protein levels by p53 over- expression due to either transient transfection of exogenous p53 or induction of endogenous p53. p53 over-expression represses androgen-induced transactivation of NKX3.1 by inhibiting the promoter of the androgen acceptor (AR) gene and by blocking AR-DNA binding activity. In addition, transfection with the p21 expression vector (pPSA-p21) showed that p21 does not reduce NKX3.1 expression, indicating that NKX3.1 expression is not the result of nonspecific effects of cell growth arrest. Our results provide biochemical and cellular biologic evidence that NKX3.1 is down-regulated by p53 over-expression in prostate cancer cells.

Keyword

androgens; gene expression regulation; NKX3.1 protein; human; prostate neoplasms; p53

MeSH Terms

Tumor Suppressor Protein p53/genetics/*metabolism
Transcription Factors/genetics/*metabolism
Trans-Activation (Genetics)/drug effects
Response Elements
RNA, Messenger/genetics
Prostatic Neoplasms/genetics/*metabolism
Promoter Regions (Genetics)/genetics
Plasmids/genetics
Male
Humans
Homeodomain Proteins/genetics/*metabolism
Genes, Reporter/genetics
Down-Regulation
Cell Line, Tumor
Androgens/*pharmacology